Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols

<p>Abstract</p> <p>Background</p> <p>The study was designed to test the hypothesis that granulosa cell (GC) gene expression response differs between recombinant FSH and human menopausal gonadotropin (hMG) stimulation regimens.</p> <p>Methods</p> <p>Females < 35 years-old undergoing IVF for tubal or male factor infertility were prospectively randomized to one of two stimulation protocols, GnRH agonist long protocol plus individualized dosages of (1) recombinant (r)FSH (Gonal-F) or (2) purified human menopausal gonadotropin (hMG; Menopur). Oocytes were retrieved 35 h post-hCG, and GC were collected. Total RNA was extracted from each GC sample, biotinylated cRNA was synthesized, and each sample was run on Human Genome Bioarrays (Applied Microarrays). Unnamed genes and genes with <2-fold difference in expression were excluded.</p> <p>Results</p> <p>After exclusions, 1736 genes exhibited differential expression between groups. Over 400 were categorized as signal transduction genes, ~180 as transcriptional regulators, and ~175 as enzymes/metabolic genes. Expression of selected genes was confirmed by RT-PCR. Differentially expressed genes included A kinase anchor protein 11 (AKAP11), bone morphogenetic protein receptor II (BMPR2), epidermal growth factor (EGF), insulin-like growth factor binding protein (IGFBP)-4, IGFBP-5, and hypoxia-inducible factor (HIF)-1 alpha.</p> <p>Conclusions</p> <p>Results suggest that major differences exist in the mechanism by which pure FSH alone versus FSH/LH regulate gene expression in preovulatory GC that could impact oocyte maturity and developmental competence.</p

Neural and Synaptic Defects in slytherin, a Zebrafish Model for Human Congenital Disorders of Glycosylation

Congenital disorder of glycosylation type IIc (CDG IIc) is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn), which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS), the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent. We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development

A Combination of Dopamine Genes Predicts Success by Professional Wall Street Traders

What determines success on Wall Street? This study examined if genes affecting dopamine levels of professional traders were associated with their career tenure. Sixty professional Wall Street traders were genotyped and compared to a control group who did not trade stocks. We found that distinct alleles of the dopamine receptor 4 promoter (DRD4P) and catecholamine-O-methyltransferase (COMT) that affect synaptic dopamine were predominant in traders. These alleles are associated with moderate, rather than very high or very low, levels of synaptic dopamine. The activity of these alleles correlated positively with years spent trading stocks on Wall Street. Differences in personality and trading behavior were also correlated with allelic variants. This evidence suggests there may be a genetic basis for the traits that make one a successful trader

Complex Interplay of Evolutionary Forces in the ladybird Homeobox Genes of Drosophila melanogaster

Tandemly arranged paralogous genes lbe and lbl are members of the Drosophila NK homeobox family. We analyzed population samples of Drosophila melanogaster from Africa, Europe, North and South America, and single strains of D. sechellia, D. simulans, and D. yakuba within two linked regions encompassing partial sequences of lbe and lbl. The evolution of lbe and lbl is highly constrained due to their important regulatory functions. Despite this, a variety of forces have shaped the patterns of variation in lb genes: recombination, intragenic gene conversion and natural selection strongly influence background variation created by linkage disequilibrium and dimorphic haplotype structure. The two genes exhibited similar levels of nucleotide diversity and positive selection was detected in the noncoding regions of both genes. However, synonymous variability was significantly higher for lbe: no nonsynonymous changes were observed in this gene. We argue that balancing selection impacts some synonymous sites of the lbe gene. Stability of mRNA secondary structure was significantly different between the lbe (but not lbl) haplotype groups and may represent a driving force of balancing selection in epistatically interacting synonymous sites. Balancing selection on synonymous sites may be the first, or one of a few such observations, in Drosophila. In contrast, recurrent positive selection on lbl at the protein level influenced evolution at three codon sites. Transcription factor binding-site profiles were different for lbe and lbl, suggesting that their developmental functions are not redundant. Combined with our previous results on nucleotide variation in esterase and other homeobox genes, these results suggest that interplay of balancing and directional selection may be a general feature of molecular evolution in Drosophila and other eukaryote genomes

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Eine Momentaufnahme der empirischen Dramatherapieforschung: Ein Literaturüberblick

The North American Drama Therapy Association (NADTA) defines drama therapy as the intentional use of drama and theatre processes to achieve therapeutic goals. As a growing field, the profession of drama therapy continues to encounter challenges and barriers to proliferation in North America. A comprehensive understanding of the scope of the empirical literature to date may help drama therapists strengthen their evidence-based practices and support the growth of the profession. This general review of drama therapy literature provides an overview of the existing empirical drama therapy research to date. Building on a review project undertaken by the NADTA research committee in 2017, this article attempts to answer the question: What empirical research exists about drama therapy? To guide this process, authors established a working definition of "empirical research" and set inclusion criteria for relevant research. Through extensive database searches, a total of 89 articles were identified. These findings were organized into three main categories and 39 sub-categories. The categories identified were: drama therapy intervention and assessment (16 sub-categories), special populations and special contexts (18 sub-categories), and the profession of drama therapy (five sub-categories). A summary of the findings is presented and discussed.Die Nordamerikanische Drama Therapy Association (NADTA) definiert Dramatherapie als den bewussten Einsatz von Drama- und Theaterprozessen zur Erreichung therapeutischer Ziele. Als wachsendes Gebiet sieht sich das Berufsfeld der Dramatherapie (im Deutschen: Theatertherapie) weiterhin mit Herausforderungen und Barrieren der Verbreitung konfrontiert. Ein umfassendes Verständnis des Umfangs der bisherigen empirischen Literatur kann Drama- und Theatertherapeut*innen helfen, ihre evidenzbasierten Praxis zu stärken und das Wachstum des Berufs zu unterstützen. Diese allgemeine Literaturübersicht gibt einen Überblick über die derzeit vorliegende empirische Dramatherapieforschung. Aufbauend auf einem Literaturüberblick des NADTA-Forschungsausschusses im Jahr 2017 versucht dieser Artikel zu sammeln, welche empirischen Untersuchungen zur Dramatherapie vorliegen. Zur Steuerung dieses Prozesses haben die Autoren eine Arbeitsdefinition für "empirischen Forschung" erstellt und Einschlusskriterien für relevante Forschung festgelegt. Durch umfangreiche Datenbankrecherchen wurden insgesamt 89 Artikel identifiziert. Die Ergebnisse wurden in drei Hauptkategorien und 39 Unterkategorien eingeteilt. Die Kategorien waren: (a) Intervention und Bewertung der Theatertherapie (16 Subkategorien), (b) spezielle Populationen und spezielle Kontexte (18 Subkategorien) und (c) der Beruf der Theatertherapie (fünf Subkategorien). Die Ergebnisse werden dargestellt und diskutiert